Citations

Copper-laden Bedlington terriers were found to absorb copper normally, based on the ratio of 64Cu in bile and in plasma ceruloplasmin after oral and intravenous doses of the radionuclide. The excessive accumulation of the copper in Bedlington terriers was due to impaired biliary excretion of the metal, The abnormal Bedlington pattern was simulated in normal dogs by biliary obstruction. Although the Bedlington terriers excreted more copper in their urine than normal, the amount was far less than that accumulated secondary to inadequate biliary excretion. These abnormalities are shared by patients with Wilson's disease, both conditions being inherited on an autosomal recessive basis. copper absorption; copper excretion; radiocopper; Wilson's disease Submitted on May 5, 1981 Accepted on March 30, 1982

About 100 µg of copper as cupric acetate-Cu64 was given iv to adult, male rats. Maximal concentrations of Cu64 were reached quickly in the excretory organs—liver, kidney, and gastrointestinal tract—which then slowly released their radioactivity. In most of the other organs a progressive accumulation of Cu64 began after the disappearance of most of the nonceruloplasminic Cu64 from the plasma and after ceruloplasmin-Cu64 emerged in the plasma, suggesting that ceruloplasmin may be the copper donor for the tissues. The disappearance of plasmatic Cu64 tended to parallel that from the liver after the first 48 hr.

The concentrations of copper in organs of white male rats were measured. Highest concentrations were in the kidney (5.1 µg/g wet wt.), liver (4.4), heart (4.5), and pituitary (about 5). Hair contained about 30 µg/g. From the weights of the organs and their copper concentrations, the total copper contents of the organs and of the whole rat were calculated. The whole rat (250 g) contained slightly less than 0.5 mg, of which about half was in the skin and muscle. Balance studies indicated that approximately 300 µg of copper was excreted daily, almost exclusively in the feces. Relatively small amounts of copper were excreted in urine. When expressed as proportion of body weight, the weights of testes, pancreas, skin, and eyes were larger in the rat than in man, and adrenals, brain, and thyroid were considerably smaller.

Varying doses of Cu64-labeled cupric acetate were given orally or intravenously to adult male rats. The urinary and fecal excretion of Cu64 was measured in intact rats and in rats with obstruction of the common duct. In addition, the biliary Cu64 was assayed in rats with biliary fistula. Only about half to two-thirds of doses up to 1 µg of copper were absorbed; the site of absorption seemed to be the upper portion of the small intestine. With larger doses, the percentage absorbed fell, but the absolute amount increased. Much less copper was excreted in the feces when the rat had a biliary fistula, the difference being accounted for by the biliary Cu64. Fecal excretion was not prevented by duodenostomy below the pancreatic and biliary ducts and therefore presumably reflects excretion through the gut mucosa. Significantly more copper was excreted in the bile and in the urine when the Cu64 was given intravenously. Very little of the biliary Cu64 was absorbed from the gut of intact rats when it was given by stomach tube.